Nah, having it installed on a secondary hdd shouldn't have any effect what so ever. Unless, if its a USB hdd your talking about then yes, it probably will have a problem running the game (I've heard nothing good about USB drives)

Have you tried re-installing the game?
Updating drivers (Graphics,Sound etc...)
Latest version of Direct X?

Also try disabling as many programs as possible while running the game, they tend to interfere.